We will continue to study the immunobiology of antiserum-dependent, cell-mediated destruction of neoplastic cells. As we demonstrated previously, lymphoid cells from nonsensitized syngeneic mice and decomplemented antiserum from tumor-immune mice interact to produce specific killing of tumor cells in a microcytotoxicity assay in vitro. Cytotoxicity does not occur in the presence of either the antiserum or effector cells alone. We propose to continue our in vitro studies of this phenomenon and to investigate the in vivo role of antiserum-dependent cellular cytotoxicity (ADC) in the anti-tumor immune response. Specifically, we will: (1) Further characterize the effector (killer) cells which mediate ADC to tumor targets. Specific immunoadsorbent columns, adherence columns and specific antisera will be used to purify K cells. Their morphology and ability to mediate ADC to different types of target cells in CR51 release and microcytotoxicity assays will be studied. (2) Further characterize the serum factors which induce ADC. We have established that two factors induce ADC: one is specific IgG antibody; the other factor appears early in the immune response and is apparently neither IgG nor IgM. The molecular nature of this second factor and its synthesis during a primary immune response in vitro will be studied. (3) Extend our current models and develop new ones for in vivo immunotherapy and immunoprophylaxis. Both chemically (3-methylcholanthrene) and virally (Moloney sarcoma virus) induced tumors will be used in experiments to determine what role ADC plays in vivo. Specific antibody plus K cells will be used in attempts to influence the course of tumor growth and to prevent metastasis.